The baculovirus antiapoptotic protein p35 inhibited the proteolytic activity of human interleukin-1 beta converting enzyme (ICD) and three of its homologs in enzymatic assays. Coexpression of p35 prevented the autoproteolytic activation on ICE from its precursor form and blocked ICE-induced apoptosis, Inhibition of enzymatic activity correlated with the cleavage of p35 and the formation of a stable ICE-p35 complex. The ability of p35 to block apoptosis in different pathways and in distantly related organisms suggests a central and conserved role for ICE-like proteases in the induction of apoptosis.